Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients with Isolated Systolic Hypertension and Left Ventricular Hypertrophy - Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients with Isolated Systolic Hypertension and Left Ventricular Hypertrophy.

Oct 30, 2002
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Date Presented:
01/01/2002
Date Published:
01/01/2002
Date Updated:
10/30/2002
Original Posted Date:
10/30/2002
References

Description:

Is the angiotensin receptor blocker (ARB) losartan more effective than atenolol at reducing CV events in patients with isolated systolic hypertension (ISH) associated with left ventricular hypertrophy (LVH)?

Study Design

Study Design:

Patients Enrolled: 1326
Mean Patient Age: 55-88

Drug/Procedures Used:

A randomized double blind parallel study comparing losartan to atenolol in 1326 men and women with ISH and ECG LVH aged 55-80 years. The primary endpoint was CV death, stroke or MI. Entry BP criteria was a systolic pressure 160-200mmHg and diastolic BP <90 mmHg. LVH was determined by ECG criteria. Fifty to 100mg of losartan or atenolol could be supplemented with 12.5-25 mg of HCTZ to achieve a goal systolic BP <140 mmHg over the first six months, and other antihypertensives were mandated after 6 mo if SBP remained above 160 mmHg.

Principal Findings:

There were no between group differences in the following at baseline: mean age of 70 years, 60% women, 90% white, 15% smokers, 22% coronary disease, 11% cerebral vascular disease, 8% PVOD, and 17% diabetes. 32% were previously treated for ISH. Mean entry BP was 174/83 mmHg. The mean blood pressure reduction was identical in both groups (28/9 mmHg). On treatment BP averaged 146/75 mmHg, pulse pressure 71 mmHg on losartan and 73 mmHg on atenolol (p = 0.07), and mean pressure 98mmHg. The ECG LVH measure was reduced more by losartan than atenolol. The primary composite endpoint occurred 25% less often with losartan. CV mortality and stroke rate decreased early with losartan, but there was no difference in MI during followup. Adjustment for BP did not change the results. There was a lower incidence of new diabetes with losartan and a lower total mortality, and the advantage of losartan was present in diabetics and non-diabetics. Losartan was better tolerated with fewer discontinuations.

Interpretation:

Losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH. This is an important study, but leaves much unanswered because we don't just treat the blood pressure. There is no data on lipids, use of ASA or statins, and whether the results are comparable in those with and without previous cardiovascular disease. Nevertheless, the ARBs are better tolerated and more effective than beta-blockers for preventing stroke and total mortality. That they are not better than beta-blockers for preventing MI, further supporting a role for beta blockade in CHD with hypertension.

References:

JAMA 2002;288:1491-98

Keywords: Hypertrophy, Left Ventricular, Losartan, Angiotensin Receptor Antagonists, Stroke, Lipids, Coronary Disease, Blood Pressure, Electrocardiography, Hydrochlorothiazide, Diabetes Mellitus, Hypertension


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